Phagocytes, NADPH oxydases et immunogénétique dans l’inflammation systémique
Team El Benna
Department Nephrology, Immunology and Hematology
Our team is interested in studying molecular and cellular mechanisms of inflammation, focusing on the regulationof the main reactive oxygen species (ROS) producing enzymes, the NADPH oxidases (NOXs) and their role in thephysiopathology of inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). When their production is controlled, reactive oxygen species (ROS) are involved in many important physiological functions. Thus ROS produced by the phagocyte NADPH oxidase, NOX2, in neutrophils, monocytes and macrophages are required for their bactericidal function, and importantly in dendritic cells, NOX2 has a critical role in antigen cross-presentation. Homologues of NOX2, such as NOX1, are also expressed in epithelial cells, but their physiological role is not fully understood. On the other hand, it is clear that excessive or inappropriate ROS production can induce severe tissue injury that participates to the physiopathology of inflammatory diseases. Deciphering mechanisms underlying activation of NOX2 in phagocytes and NOX1 in epithelial cells is essential to identify novel therapeutic targets in inflammation. The projects of the team aim to understand the regulation of NOX2 in neutrophils, monocytes/macrophages and dendritic cells and NOX1 in epithelial cells by pro- and anti-inflammatory agents; and to translate our basic research to animal models of inflammation, human phagocytic disorders and human inflammatory diseases. Our project combines basic and clinical research and involves several collaborations with teams in the Center for Research on Inflammation (CRI) and Bichat hospital divisions.
Principal research axis:
Our work is conducted following three main axis : 1)-To understand the regulation of the NADPH oxidases NOX in neutrophils, monocytes, macrophages, dendritic cells and epithelial cells in response to pro- and anti-inflammatory agents. 2)-To study polymorphism of NOX and regulators and identify new genetic factors involved in systemic inflammation. 3-To study the role of the NOX2, NOX1 and newly identified proteins in inflammatory process: by investigating their activation in phagocytic disorders, human inflammatory diseases and in animal models of inflammation.
Publication date : 01 July 2020 More
Innate immune cells in cirrhosis J Hepatol
Autors : Christine Bernsmeier Schalk van der Merwe Perianin Axel
Publication date : 22 January 2020 More
The dual role of ROS-generating NADPH oxidases in gastrointestinal inflammation and therapeutic perspectives. Antioxidants & Redox Signaling. 2020 Jan 22
Autors : Dang Pham My-Chan Rolas L El Benna Jamel
Publication date : 01 November 2019 More
The prolyl isomerase Pin1 controls lipopolysaccharide-induced priming of NADPH oxidase in human neutrophils. Frontiers In Immunology Frontiers In Immunology (sous presse).
Autors : Liu Min Bedouhene Samia Hurtado-Nedelec Maria Margarita Pintard Coralie Dang Pham My-Chan Yu S El Benna Jamel
Publication date : 06 September 2019 More
Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils. J Exp Med. 2019 Sep 6. pii: jem.20180371.
Autors : Ohayon D De Chiara A Dang Pham My-Chan Thieblemont N Chatfield S Marzaioli V Burgener SS Mocek J Candalh C Pintard Coralie Tacnet-Delorme P Renault G Lagoutte I Favier M Walker Francine Hurtado-Nedelec Maria Margarita Desplancq D Weiss Emmanuel Benarafa C Housset D Marie Jean-Claude Frachet P El Benna Jamel Witko-Sarsat V
Publication date : 01 March 2019 More
The Kinesin Light Chain-Related Protein PAT1 Promotes Superoxide Anion Production in Human Phagocytes. J Immunol. 2019 Mar 1;202(5):1549-1558
Autors : Arabi-Derkawi R O'Dowd Y Cheng N Rolas L Boussetta T Raad H Marzaioli V Pintard Coralie Fasseu M Kroviarski Y Belambri SA Dang Pham My-Chan Ye RD Gougerot-Pocidalo Marie-Anne El Benna Jamel
Publication date : 02 October 2018 More
NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions Mucosal Immunology, 2018 Oct doi: 10.1038/s41385-018-0086-4.
Autors : Makhezer N Ben-Khemis Marwah Liu Dan Khichane Y Marzaioli V Tlili A Mojallali Marjan Pintard Coralie Letteron Philippe Hurtado-Nedelec Maria Margarita El Benna Jamel Marie Jean-Claude Sannier A Pelletier Anne-Laure Dang Pham My-Chan
Publication date : 09 July 2018 More
NADPH oxidase depletion in neutrophils from patients with cirrhosis and restoration via toll-like receptor 7/8 activation Gut. 2018;67(8):1505-1516
Autors : Rolas L Boussif A Weiss Emmanuel Letteron Philippe Haddad O El Benna Jamel Rautou Pierre-Emmanuel Moreau Richard Perianin Axel
Publication date : 12 October 2017 More
NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells. Blood. 2017 Oct 12;130(15):1734-1745
Autors : Marzaioli V Hurtado-Nedelec Maria Margarita Pintard Coralie Tlili A Marie Jean-Claude Monteiro RC Gougerot-Pocidalo Marie-Anne Dang Pham My-Chan El Benna Jamel
Publication date : 01 March 2017 More
Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47(phox) phosphorylation pathway in monocytes Mucosal Immunology, 2017 Mar;10(2):332-340
Autors : Chedid P Boussetta T Dang Pham My-Chan Belambri SA Marzaioli V, Fasseau M Walker Francine Couvineau Alain El Benna Jamel Marie Jean-Claude